ZA200406032B - Dihydrobenzodiazepin-2-one derivatives for the treatment of neurological disorders. - Google Patents
Dihydrobenzodiazepin-2-one derivatives for the treatment of neurological disorders. Download PDFInfo
- Publication number
- ZA200406032B ZA200406032B ZA200406032A ZA200406032A ZA200406032B ZA 200406032 B ZA200406032 B ZA 200406032B ZA 200406032 A ZA200406032 A ZA 200406032A ZA 200406032 A ZA200406032 A ZA 200406032A ZA 200406032 B ZA200406032 B ZA 200406032B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- diazepin
- benzo
- dihydro
- pyridin
- Prior art date
Links
- 208000012902 Nervous system disease Diseases 0.000 title claims description 5
- 208000025966 Neurological disease Diseases 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 117
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 125000003545 alkoxy group Chemical group 0.000 claims description 51
- -1 -NR’R” Chemical group 0.000 claims description 43
- 125000003282 alkyl amino group Chemical group 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 150000002367 halogens Chemical group 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000001153 fluoro group Chemical group F* 0.000 claims description 18
- AZIZBYRGIGKTLW-UHFFFAOYSA-N 1,4-diazepin-2-one Chemical compound O=C1C=NC=CC=N1 AZIZBYRGIGKTLW-UHFFFAOYSA-N 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- QDKZHQGXPVFLHU-UHFFFAOYSA-N 1,5-benzodiazepin-2-one Chemical compound O=C1C=CN=C2C=CC=CC2=N1 QDKZHQGXPVFLHU-UHFFFAOYSA-N 0.000 claims description 10
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000026139 Memory disease Diseases 0.000 claims description 4
- 208000028017 Psychotic disease Diseases 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- 208000010877 cognitive disease Diseases 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- XTQHVAXLUHGINO-UHFFFAOYSA-N 4-(3-pyridin-3-ylphenyl)-7-(2,2,2-trifluoroethoxy)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C2=CC(OCC(F)(F)F)=CC=C2NC(=O)CC=1C(C=1)=CC=CC=1C1=CC=CN=C1 XTQHVAXLUHGINO-UHFFFAOYSA-N 0.000 claims description 2
- XFCBAUSXXGLTIP-UHFFFAOYSA-N 4-(3-pyridin-3-ylphenyl)-7-(2,2,2-trifluoroethoxy)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC(F)(F)F)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=CN=C1 XFCBAUSXXGLTIP-UHFFFAOYSA-N 0.000 claims description 2
- JYTRCRINABXASK-UHFFFAOYSA-N 4-(3-pyridin-4-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC2=CC(C(F)(F)F)=CC=C2N=C1C(C=1)=CC=CC=1C1=CC=NC=C1 JYTRCRINABXASK-UHFFFAOYSA-N 0.000 claims description 2
- GGCAJGPNBPIIQA-UHFFFAOYSA-N 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-7-ethoxy-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NC(C)=C1 GGCAJGPNBPIIQA-UHFFFAOYSA-N 0.000 claims description 2
- PQWNWLVSPGJPAF-UHFFFAOYSA-N 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)C(F)(F)F)=C1 PQWNWLVSPGJPAF-UHFFFAOYSA-N 0.000 claims description 2
- CHTAULFZQPVWNJ-UHFFFAOYSA-N 4-[3-(2-ethylpyridin-4-yl)phenyl]-7-methyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(CC)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(C)C=C3N=2)C(F)(F)F)=C1 CHTAULFZQPVWNJ-UHFFFAOYSA-N 0.000 claims description 2
- XRLZWRIHQVVACZ-UHFFFAOYSA-N 4-[3-(2-methylpyridin-4-yl)phenyl]-8-(trifluoromethoxy)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(OC(F)(F)F)=CC=C3N=2)=C1 XRLZWRIHQVVACZ-UHFFFAOYSA-N 0.000 claims description 2
- PBXFRAFAGCEVSF-UHFFFAOYSA-N 4-[3-(6-cyclopropylpyridin-3-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC2=CC(C(F)(F)F)=CC=C2N=C1C(C=1)=CC=CC=1C(C=N1)=CC=C1C1CC1 PBXFRAFAGCEVSF-UHFFFAOYSA-N 0.000 claims description 2
- VMEZSFFCHLCBBK-UHFFFAOYSA-N 7,8-dichloro-4-(3-pyridin-4-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(Cl)C(Cl)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1C1=CC=NC=C1 VMEZSFFCHLCBBK-UHFFFAOYSA-N 0.000 claims description 2
- HXTQTHUBKDBECJ-UHFFFAOYSA-N 7,8-dichloro-4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(Cl)=C(Cl)C=C3N=2)=C1 HXTQTHUBKDBECJ-UHFFFAOYSA-N 0.000 claims description 2
- DZCFLWXSUXKAJI-UHFFFAOYSA-N 7-(dimethylamino)-4-(3-pyridin-3-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=CN=C1 DZCFLWXSUXKAJI-UHFFFAOYSA-N 0.000 claims description 2
- YQKASQGOPRPMLH-UHFFFAOYSA-N 7-(dimethylamino)-4-(3-pyridin-4-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NC=C1 YQKASQGOPRPMLH-UHFFFAOYSA-N 0.000 claims description 2
- CCOJJDFNFUBNKN-UHFFFAOYSA-N 7-(dimethylamino)-4-[3-(2-methylpyridin-4-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NC(C)=C1 CCOJJDFNFUBNKN-UHFFFAOYSA-N 0.000 claims description 2
- AHDAHZZDQMCLJT-UHFFFAOYSA-N 7-chloro-4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(Cl)C=C3N=2)C(F)(F)F)=C1 AHDAHZZDQMCLJT-UHFFFAOYSA-N 0.000 claims description 2
- QFBDRSIFOKYSDY-UHFFFAOYSA-N 7-ethoxy-4-(3-pyridin-4-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NC=C1 QFBDRSIFOKYSDY-UHFFFAOYSA-N 0.000 claims description 2
- QCDLBZFFNJYTAV-UHFFFAOYSA-N 7-ethyl-4-[3-(2-methylpyridin-4-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(CC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NC(C)=C1 QCDLBZFFNJYTAV-UHFFFAOYSA-N 0.000 claims description 2
- OQTSPIQICMTNOL-UHFFFAOYSA-N 7-methyl-4-(3-pyridazin-4-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NN=C1 OQTSPIQICMTNOL-UHFFFAOYSA-N 0.000 claims description 2
- NZWUYDARLBVUAZ-UHFFFAOYSA-N 8-(2-fluorophenyl)-4-(3-pyridin-3-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound FC1=CC=CC=C1C1=CC=C(N=C(CC(=O)N2)C=3C=C(C=CC=3)C=3C=NC=CC=3)C2=C1 NZWUYDARLBVUAZ-UHFFFAOYSA-N 0.000 claims description 2
- DEOUQGPUEWWMNC-UHFFFAOYSA-N 8-(2-fluorophenyl)-4-(3-pyridin-4-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound FC1=CC=CC=C1C1=CC=C(N=C(CC(=O)N2)C=3C=C(C=CC=3)C=3C=CN=CC=3)C2=C1 DEOUQGPUEWWMNC-UHFFFAOYSA-N 0.000 claims description 2
- VBTRNVBPGJSEAM-UHFFFAOYSA-N 8-(2-fluorophenyl)-4-(3-pyrimidin-5-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound FC1=CC=CC=C1C1=CC=C(N=C(CC(=O)N2)C=3C=C(C=CC=3)C=3C=NC=NC=3)C2=C1 VBTRNVBPGJSEAM-UHFFFAOYSA-N 0.000 claims description 2
- LKVQKLAWCNGKSL-UHFFFAOYSA-N 8-(2-fluorophenyl)-4-[3-(2-methylpyridin-4-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)C=2C(=CC=CC=2)F)=C1 LKVQKLAWCNGKSL-UHFFFAOYSA-N 0.000 claims description 2
- RRJHUDLALLDKRL-UHFFFAOYSA-N 8-chloro-4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-7-methyl-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(Cl)=C(C)C=C3N=2)=C1 RRJHUDLALLDKRL-UHFFFAOYSA-N 0.000 claims description 2
- JLXAVOQTRVUYKG-UHFFFAOYSA-N 8-chloro-4-[3-(2-methylpyridin-3-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC=CC=C1C1=CC=CC(C=2CC(=O)NC3=CC(Cl)=CC=C3N=2)=C1 JLXAVOQTRVUYKG-UHFFFAOYSA-N 0.000 claims description 2
- PRPOBZJPAWDSGQ-UHFFFAOYSA-N 8-chloro-4-[3-(2-methylpyridin-4-yl)phenyl]-7-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(Cl)=C(C=C3N=2)C(F)(F)F)=C1 PRPOBZJPAWDSGQ-UHFFFAOYSA-N 0.000 claims description 2
- VOUQMUWKUYFRJK-UHFFFAOYSA-N 8-chloro-4-[3-(6-methylpyridin-3-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC=C1C1=CC=CC(C=2CC(=O)NC3=CC(Cl)=CC=C3N=2)=C1 VOUQMUWKUYFRJK-UHFFFAOYSA-N 0.000 claims description 2
- ITPMBZMJFFOBBB-UHFFFAOYSA-N 8-chloro-7-methyl-4-(3-pyridazin-4-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NN=C1 ITPMBZMJFFOBBB-UHFFFAOYSA-N 0.000 claims description 2
- QPHSKVNFGZIDPN-UHFFFAOYSA-N 8-chloro-7-methyl-4-(3-pyridin-4-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NC=C1 QPHSKVNFGZIDPN-UHFFFAOYSA-N 0.000 claims description 2
- CWZIXKLALYDKHJ-UHFFFAOYSA-N 8-chloro-7-methyl-4-[3-(2-methylpyridin-4-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(Cl)=C(C)C=C3N=2)=C1 CWZIXKLALYDKHJ-UHFFFAOYSA-N 0.000 claims description 2
- YJSYRZKLIDMQGG-UHFFFAOYSA-N 8-fluoro-4-[3-(2-methylpyridin-4-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(F)=CC=C3N=2)=C1 YJSYRZKLIDMQGG-UHFFFAOYSA-N 0.000 claims description 2
- QRDOMCFVXRYHRK-UHFFFAOYSA-N 8-methyl-4-(3-pyridin-4-ylphenyl)-7-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(C(F)(F)F)C(C)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1C1=CC=NC=C1 QRDOMCFVXRYHRK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- LYTVXCQQTLUEQR-UHFFFAOYSA-N ro4491533 Chemical compound CC1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(C)C=C3N=2)C(F)(F)F)=C1 LYTVXCQQTLUEQR-UHFFFAOYSA-N 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 9
- 239000000126 substance Substances 0.000 claims 8
- 230000006806 disease prevention Effects 0.000 claims 3
- UVNQIBJKZJJBQK-UHFFFAOYSA-N 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-7-ethyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(CC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC(C)=NC(C)=C1 UVNQIBJKZJJBQK-UHFFFAOYSA-N 0.000 claims 1
- CLEXCUYVRGOQCW-UHFFFAOYSA-N 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-8-methyl-7-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(C)=C(C=C3N=2)C(F)(F)F)=C1 CLEXCUYVRGOQCW-UHFFFAOYSA-N 0.000 claims 1
- AFSJGBXRHLXBHV-UHFFFAOYSA-N 4-[3-(2-ethyl-6-methylpyridin-4-yl)phenyl]-7-methyl-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC(CC)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(C)C=C3N=2)C(F)(F)F)=C1 AFSJGBXRHLXBHV-UHFFFAOYSA-N 0.000 claims 1
- MTRZSMDLMJKFMC-UHFFFAOYSA-N 4-[3-(6-methylpyrimidin-4-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=CC=C3N=2)C(F)(F)F)=N1 MTRZSMDLMJKFMC-UHFFFAOYSA-N 0.000 claims 1
- CUBHTWLIWFXCKK-UHFFFAOYSA-N 7,8-dichloro-4-(3-pyridin-3-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(Cl)C(Cl)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1C1=CC=CN=C1 CUBHTWLIWFXCKK-UHFFFAOYSA-N 0.000 claims 1
- UJVWWZXXZMKDKY-UHFFFAOYSA-N 7,8-dichloro-4-[3-(2-methylpyridin-4-yl)phenyl]-2,3-dihydro-1H-1,5-benzodiazepine Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CCNC3=CC(Cl)=C(Cl)C=C3N=2)=C1 UJVWWZXXZMKDKY-UHFFFAOYSA-N 0.000 claims 1
- BAXARIOGPJRTLH-UHFFFAOYSA-N 7-(cyclopropylmethoxy)-4-[3-(2-methylpyridin-4-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(OCC4CC4)C=C3N=2)C(F)(F)F)=C1 BAXARIOGPJRTLH-UHFFFAOYSA-N 0.000 claims 1
- GXQISOFEZQYHPI-UHFFFAOYSA-N 7-[methyl(propyl)amino]-4-(3-pyrazin-2-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(N(C)CCC)=CC=2N=C1C(C=1)=CC=CC=1C1=CN=CC=N1 GXQISOFEZQYHPI-UHFFFAOYSA-N 0.000 claims 1
- OPUCFSUMZCYZKN-UHFFFAOYSA-N 7-chloro-4-(3-pyridin-4-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(Cl)C(C(F)(F)F)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1C1=CC=NC=C1 OPUCFSUMZCYZKN-UHFFFAOYSA-N 0.000 claims 1
- XJKJJKMFTRWVGB-UHFFFAOYSA-N 7-methoxy-4-(3-pyridin-3-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=CN=C1 XJKJJKMFTRWVGB-UHFFFAOYSA-N 0.000 claims 1
- ZTMGYWMZJBHXBD-UHFFFAOYSA-N 7-methyl-4-[3-(2-methylpyridin-4-yl)phenyl]-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(=C(C)C=C3N=2)C(F)(F)F)=C1 ZTMGYWMZJBHXBD-UHFFFAOYSA-N 0.000 claims 1
- QHWRKFWOOXWYMW-UHFFFAOYSA-N 8-(2-fluorophenyl)-4-[3-(2-methylpyridin-3-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound CC1=NC=CC=C1C1=CC=CC(C=2CC(=O)NC3=CC(=CC=C3N=2)C=2C(=CC=CC=2)F)=C1 QHWRKFWOOXWYMW-UHFFFAOYSA-N 0.000 claims 1
- HRSCABPISYBZJE-UHFFFAOYSA-N 8-chloro-7-methyl-4-(3-pyrazin-2-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(C)=CC=2N=C1C(C=1)=CC=CC=1C1=CN=CC=N1 HRSCABPISYBZJE-UHFFFAOYSA-N 0.000 claims 1
- ODSWASRHKDESDR-UHFFFAOYSA-N 8-chloro-7-methyl-4-(3-pyridin-3-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(Cl)C(C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=CN=C1 ODSWASRHKDESDR-UHFFFAOYSA-N 0.000 claims 1
- YYEKPNNSPXLPJC-UHFFFAOYSA-N 8-methyl-4-(3-pyridin-3-ylphenyl)-7-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N=1C=2C=C(C(F)(F)F)C(C)=CC=2NC(=O)CC=1C(C=1)=CC=CC=1C1=CC=CN=C1 YYEKPNNSPXLPJC-UHFFFAOYSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 6
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 6
- 239000000010 aprotic solvent Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 150000002926 oxygen Chemical class 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 2
- VUNAQOGRLGNALG-UHFFFAOYSA-N 2-chloro-5-nitrobenzene-1,4-diamine Chemical compound NC1=CC([N+]([O-])=O)=C(N)C=C1Cl VUNAQOGRLGNALG-UHFFFAOYSA-N 0.000 description 2
- DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical class NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 239000007848 Bronsted acid Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 208000027089 Parkinsonian disease Diseases 0.000 description 2
- 206010034010 Parkinsonism Diseases 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- LDCMTXMRTVOLKA-UHFFFAOYSA-N 1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound N1C(=O)CC=NC2=CC=CC=C21 LDCMTXMRTVOLKA-UHFFFAOYSA-N 0.000 description 1
- ODRZAZBEQWAOGU-UHFFFAOYSA-N 1,4-dioxin-2-one Chemical compound O=C1COC=CO1 ODRZAZBEQWAOGU-UHFFFAOYSA-N 0.000 description 1
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical class COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 1
- JFPJVTNYCURRAB-UHFFFAOYSA-N 2-nitro-n-phenylacetamide Chemical group [O-][N+](=O)CC(=O)NC1=CC=CC=C1 JFPJVTNYCURRAB-UHFFFAOYSA-N 0.000 description 1
- YJNILYRQRSSTPP-UHFFFAOYSA-N 4-(3-pyridin-3-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC2=CC(C(F)(F)F)=CC=C2N=C1C(C=1)=CC=CC=1C1=CC=CN=C1 YJNILYRQRSSTPP-UHFFFAOYSA-N 0.000 description 1
- NBKPYZLFZCYJJE-UHFFFAOYSA-N 4-(3-pyridin-4-ylphenyl)-7-(2,2,2-trifluoroethoxy)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC(F)(F)F)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NC=C1 NBKPYZLFZCYJJE-UHFFFAOYSA-N 0.000 description 1
- ZCWXYZBQDNFULS-UHFFFAOYSA-N 5-chloro-2-nitroaniline Chemical compound NC1=CC(Cl)=CC=C1[N+]([O-])=O ZCWXYZBQDNFULS-UHFFFAOYSA-N 0.000 description 1
- KWHURWOGZQWLTK-UHFFFAOYSA-N 5-chloro-4-iodo-2-nitroaniline Chemical compound NC1=CC(Cl)=C(I)C=C1[N+]([O-])=O KWHURWOGZQWLTK-UHFFFAOYSA-N 0.000 description 1
- CMLVJJVYIVBZNH-UHFFFAOYSA-N 7,8-dichloro-4-[3-(2-methylpyridin-4-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1=NC(C)=CC(C=2C=C(C=CC=2)C=2CC(=O)NC3=CC(Cl)=C(Cl)C=C3N=2)=C1 CMLVJJVYIVBZNH-UHFFFAOYSA-N 0.000 description 1
- RHZYZFRVSNAAOL-UHFFFAOYSA-N 7-ethoxy-4-(3-pyridin-3-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(OCC)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=CN=C1 RHZYZFRVSNAAOL-UHFFFAOYSA-N 0.000 description 1
- WLGXHFREMLNUDH-UHFFFAOYSA-N 7-methyl-4-(3-pyridin-3-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=CN=C1 WLGXHFREMLNUDH-UHFFFAOYSA-N 0.000 description 1
- ZYGZDPKEZBLAHD-UHFFFAOYSA-N 7-methyl-4-(3-pyridin-4-ylphenyl)-8-(trifluoromethyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC=2C=C(C(F)(F)F)C(C)=CC=2N=C1C(C=1)=CC=CC=1C1=CC=NC=C1 ZYGZDPKEZBLAHD-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- PQMAJJWGJPOQQE-UHFFFAOYSA-N 8-chloro-4-(3-pyridin-3-ylphenyl)-1,3-dihydro-1,5-benzodiazepin-2-one Chemical compound C1C(=O)NC2=CC(Cl)=CC=C2N=C1C(C=1)=CC=CC=1C1=CC=CN=C1 PQMAJJWGJPOQQE-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000003341 Bronsted base Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 208000020564 Eye injury Diseases 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
- 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 1
- 102100038352 Metabotropic glutamate receptor 3 Human genes 0.000 description 1
- 102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 description 1
- 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 1
- 102100038300 Metabotropic glutamate receptor 6 Human genes 0.000 description 1
- 102100038294 Metabotropic glutamate receptor 7 Human genes 0.000 description 1
- 102100037636 Metabotropic glutamate receptor 8 Human genes 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 206010057852 Nicotine dependence Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 208000026251 Opioid-Related disease Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000025569 Tobacco Use disease Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000005915 ammonolysis reaction Methods 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960004132 diethyl ether Drugs 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000003825 glutamate receptor antagonist Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 1
- 108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
- 108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 1
- 108010038450 metabotropic glutamate receptor 6 Proteins 0.000 description 1
- 108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 1
- 108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 201000005040 opiate dependence Diseases 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- UOJMTSCORVQOHS-UHFFFAOYSA-N pachypodol Natural products COc1cc(ccc1O)C2=C(C)C(=O)c3c(O)cc(C)cc3O2 UOJMTSCORVQOHS-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 210000002265 sensory receptor cell Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02002012 | 2002-02-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200406032B true ZA200406032B (en) | 2005-10-12 |
Family
ID=27675598
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200406032A ZA200406032B (en) | 2002-02-06 | 2004-07-28 | Dihydrobenzodiazepin-2-one derivatives for the treatment of neurological disorders. |
Country Status (31)
Country | Link |
---|---|
US (1) | US6949542B2 (ru) |
EP (1) | EP1474416B1 (ru) |
JP (1) | JP4077411B2 (ru) |
KR (1) | KR20040081486A (ru) |
CN (1) | CN100497333C (ru) |
AR (1) | AR038481A1 (ru) |
AT (1) | ATE374196T1 (ru) |
AU (1) | AU2003205695B8 (ru) |
BR (1) | BR0307474A (ru) |
CA (1) | CA2474219C (ru) |
DE (1) | DE60316538T2 (ru) |
DK (1) | DK1474416T3 (ru) |
ES (1) | ES2294264T3 (ru) |
GT (1) | GT200300028A (ru) |
HK (1) | HK1078858A1 (ru) |
HR (1) | HRP20040678A2 (ru) |
IL (1) | IL163102A (ru) |
MX (1) | MXPA04007516A (ru) |
MY (1) | MY176608A (ru) |
NO (1) | NO327697B1 (ru) |
NZ (1) | NZ534122A (ru) |
PA (1) | PA8565901A1 (ru) |
PE (1) | PE20031011A1 (ru) |
PL (1) | PL372425A1 (ru) |
PT (1) | PT1474416E (ru) |
RU (1) | RU2315764C2 (ru) |
SI (1) | SI1474416T1 (ru) |
TW (1) | TWI326599B (ru) |
UY (1) | UY27654A1 (ru) |
WO (1) | WO2003066623A1 (ru) |
ZA (1) | ZA200406032B (ru) |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HUP0203294A3 (en) | 1999-10-15 | 2003-03-28 | Hoffmann La Roche | Benzodiazepine derivatives, process for their preparation, pharmaceutical compositions containing them and their use |
PT1651234E (pt) * | 2003-07-25 | 2007-12-28 | Hoffmann La Roche | Combinação de um antagonista de mglur2 e de um inibidor de ache para tratamento de perturbações neurólgicas agudas e/ou crónicas |
JP5048675B2 (ja) | 2005-09-27 | 2012-10-17 | エフ.ホフマン−ラ ロシュ アーゲー | mGluR2アンタゴニストとしてのオキサジアゾリルピラゾロ−ピリミジン類 |
TWI417095B (zh) | 2006-03-15 | 2013-12-01 | Janssen Pharmaceuticals Inc | 1,4-二取代之3-氰基-吡啶酮衍生物及其作為mGluR2-受體之正向異位性調節劑之用途 |
TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
ES2369866T3 (es) * | 2007-04-19 | 2011-12-07 | F. Hoffmann-La Roche Ag | Derivados de dihidro-benzo[b][1,4]diazepin-2-ona-sulfonamida. |
CA2697167C (en) | 2007-08-27 | 2013-07-16 | F. Hoffmann-La Roche Ag | Benzimidazole derivatives used as fxr agonists |
JP5366269B2 (ja) | 2007-09-14 | 2013-12-11 | ジャンセン ファーマシューティカルズ, インコーポレイテッド. | 1,3−二置換4−(アリル−x−フェニル)−1h−ピリジン−2−オン |
KR101520086B1 (ko) | 2007-09-14 | 2015-05-14 | 얀센 파마슈티칼스 인코포레이티드 | 1´,3´-이치환된-4-페닐-3,4,5,6-테트라히드로-2h,1´h-[1,4´]비피리디닐-2´-온 |
NZ584148A (en) | 2007-09-14 | 2011-05-27 | Ortho Mcneil Janssen Pharm | 1,3-disubstituted-4-phenyl-1 h-pyridin-2-ones |
CA2704436C (en) | 2007-11-14 | 2016-01-05 | Ortho-Mcneil-Janssen Pharmaceuticals, Inc. | Imidazo[1,2-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
US8536186B2 (en) | 2008-08-04 | 2013-09-17 | Chdi Foundation, Inc. | Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
AU2009289784B2 (en) | 2008-09-02 | 2012-03-22 | Addex Pharma S.A. | 3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors |
RU2517181C2 (ru) | 2008-10-16 | 2014-05-27 | Орто-Макнейл-Янссен Фармасьютикалз, Инк. | Производные индола и бензоморфолина в качестве модулятора метаботропных глутаматных рецепторов |
CN102232074B (zh) | 2008-11-28 | 2014-12-03 | 奥梅-杨森制药有限公司 | 作为代谢性谷氨酸盐受体调节剂的吲哚和苯并噁嗪衍生物 |
MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
EA020671B1 (ru) | 2009-05-12 | 2014-12-30 | Янссен Фармасьютикалз, Инк. | ПРОИЗВОДНЫЕ 1,2,4-ТРИАЗОЛО[4,3-a]ПИРИДИНА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ПОЛОЖИТЕЛЬНЫХ АЛЛОСТЕРИЧЕСКИХ МОДУЛЯТОРОВ РЕЦЕПТОРОВ mGluR2 |
SG10201402250TA (en) | 2009-05-12 | 2014-07-30 | Janssen Pharmaceuticals Inc | 1,2,4-triazolo [4,3-a] pyridine derivatives and their use for the treatment or prevention of neurological and psychiatric disorders |
TWI481601B (zh) | 2009-08-21 | 2015-04-21 | Otsuka Pharma Co Ltd | 含氮化合物及藥學組成物 |
KR20120065360A (ko) | 2009-08-21 | 2012-06-20 | 오츠카 세이야쿠 가부시키가이샤 | 벤조[b][1,4]디아제핀-2,4-디온 화합물의 제조 방법 |
AU2011207229B2 (en) | 2010-01-25 | 2015-02-12 | Chdi Foundation, Inc. | Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
ES2552455T3 (es) | 2010-11-08 | 2015-11-30 | Janssen Pharmaceuticals, Inc. | Derivados de 1,2,4-triazolo[4,3-a]piridina y su uso como moduladores alostéricos positivos de receptores mGluR2 |
US9012448B2 (en) | 2010-11-08 | 2015-04-21 | Janssen Pharmaceuticals, Inc. | 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of MGLUR2 receptors |
WO2012149540A1 (en) | 2011-04-28 | 2012-11-01 | The Broad Institute Inc | Inhibitors of histone deacetylase |
US9193710B2 (en) | 2011-08-29 | 2015-11-24 | Sanford-Burnham Medical Research Institute | Benzodiazepinones as modulators of metabotropic glutamate receptor functions and neurological uses thereof |
KR20140072037A (ko) | 2011-08-30 | 2014-06-12 | 씨에이치디아이 파운데이션, 인코포레이티드 | 키뉴레닌-3-모노옥시게나제 억제제, 약학적 조성물 및 이의 사용 방법 |
MY166890A (en) | 2011-08-30 | 2018-07-24 | Chdi Foundation Inc | Kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof |
CA2880117C (en) | 2012-07-27 | 2021-04-06 | The Broad Institute, Inc. | Inhibitors of histone deacetylase |
SG11201503192XA (en) | 2012-10-23 | 2015-06-29 | Hoffmann La Roche | Mglu2/3 antagonists for the treatment of autistic disorders |
WO2014100438A1 (en) | 2012-12-20 | 2014-06-26 | The Broad Institute, Inc. | Cycloalkenyl hydroxamic acid derivatives and their use as histone deacetylase inhibitors |
JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
DK3096790T3 (da) | 2014-01-21 | 2019-10-07 | Janssen Pharmaceutica Nv | Kombinationer omfattende positive allosteriske modulatorer eller orthosteriske agonister af metabotrop glutamaterg subtype 2-receptor og anvendelse af disse |
CN109999033B (zh) | 2014-01-21 | 2022-12-23 | 詹森药业有限公司 | 包括代谢型谷氨酸能受体亚型2的正别构调节物或正位激动剂的组合及其用途 |
MA39901A (fr) | 2014-04-23 | 2017-03-01 | Hoffmann La Roche | Antagonistes de mglu2/3 pour le traitement de troubles des facultés intellectuelles |
US9969726B2 (en) | 2014-06-10 | 2018-05-15 | Sanford-Burnham Medical Research Institute | Metabotropic glutamate receptor negative allosteric modulators (NAMS) and uses thereof |
EA034528B1 (ru) | 2014-07-17 | 2020-02-17 | Сиэйчдиай Фаундэйшн, Инк. | Способ лечения нарушений, связанных с вич |
JP2017206438A (ja) * | 2014-08-22 | 2017-11-24 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | テトラヒドロイミダゾ[1,5−d][1,4]オキサゼピン化合物(TETRAHYDROIMIDAZO[1,5−d][1,4]OXAZEPINECOMPOUND) |
WO2018019755A1 (en) | 2016-07-26 | 2018-02-01 | Basf Se | Herbicidal pyridine compounds |
WO2018019721A1 (en) | 2016-07-26 | 2018-02-01 | Basf Se | Herbicidal pyridine compounds |
CN110407740A (zh) * | 2019-09-04 | 2019-11-05 | 上海毕得医药科技有限公司 | 一种3-溴-2-乙基吡啶的合成方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0389189B1 (en) * | 1989-03-23 | 1994-05-18 | Pfizer Limited | Diazepine antiallergy agents |
HUP0203294A3 (en) | 1999-10-15 | 2003-03-28 | Hoffmann La Roche | Benzodiazepine derivatives, process for their preparation, pharmaceutical compositions containing them and their use |
PL357418A1 (en) | 1999-10-15 | 2004-07-26 | F.Hoffmann-La Roche Ag | Benzodiazepine derivatives as metabotropic glutamate receptor antagonists |
-
2003
- 2003-01-24 US US10/350,713 patent/US6949542B2/en not_active Expired - Lifetime
- 2003-01-28 PT PT03702549T patent/PT1474416E/pt unknown
- 2003-01-28 CA CA2474219A patent/CA2474219C/en not_active Expired - Fee Related
- 2003-01-28 ES ES03702549T patent/ES2294264T3/es not_active Expired - Lifetime
- 2003-01-28 RU RU2004126945/04A patent/RU2315764C2/ru not_active IP Right Cessation
- 2003-01-28 BR BR0307474-9A patent/BR0307474A/pt not_active Application Discontinuation
- 2003-01-28 AT AT03702549T patent/ATE374196T1/de active
- 2003-01-28 EP EP03702549A patent/EP1474416B1/en not_active Expired - Lifetime
- 2003-01-28 CN CNB038065452A patent/CN100497333C/zh not_active Expired - Fee Related
- 2003-01-28 DE DE60316538T patent/DE60316538T2/de not_active Expired - Lifetime
- 2003-01-28 WO PCT/EP2003/000859 patent/WO2003066623A1/en active IP Right Grant
- 2003-01-28 SI SI200331034T patent/SI1474416T1/sl unknown
- 2003-01-28 DK DK03702549T patent/DK1474416T3/da active
- 2003-01-28 JP JP2003565996A patent/JP4077411B2/ja not_active Expired - Fee Related
- 2003-01-28 PL PL03372425A patent/PL372425A1/xx not_active Application Discontinuation
- 2003-01-28 NZ NZ534122A patent/NZ534122A/en not_active IP Right Cessation
- 2003-01-28 KR KR10-2004-7012084A patent/KR20040081486A/ko active Search and Examination
- 2003-01-28 MX MXPA04007516A patent/MXPA04007516A/es active IP Right Grant
- 2003-01-28 AU AU2003205695A patent/AU2003205695B8/en not_active Ceased
- 2003-01-30 TW TW092102234A patent/TWI326599B/zh active
- 2003-02-03 GT GT200300028A patent/GT200300028A/es unknown
- 2003-02-03 PE PE2003000122A patent/PE20031011A1/es not_active Application Discontinuation
- 2003-02-04 AR ARP030100334A patent/AR038481A1/es unknown
- 2003-02-05 PA PA20038565901A patent/PA8565901A1/es unknown
- 2003-02-05 MY MYPI20030378A patent/MY176608A/en unknown
- 2003-02-05 UY UY27654A patent/UY27654A1/es not_active Application Discontinuation
-
2004
- 2004-07-19 IL IL163102A patent/IL163102A/en not_active IP Right Cessation
- 2004-07-23 HR HR20040678A patent/HRP20040678A2/hr not_active Application Discontinuation
- 2004-07-28 ZA ZA200406032A patent/ZA200406032B/en unknown
- 2004-08-02 NO NO20043237A patent/NO327697B1/no not_active IP Right Cessation
-
2005
- 2005-11-25 HK HK05110731.8A patent/HK1078858A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA200406032B (en) | Dihydrobenzodiazepin-2-one derivatives for the treatment of neurological disorders. | |
AU2019283921B2 (en) | Indole carboxamide compounds useful as kinase inhibitors | |
JP7160688B2 (ja) | Cbp/ep300の複素環式インヒビターおよびがんの処置におけるそれらの使用 | |
KR101698631B1 (ko) | 칼륨 이온 채널 억제제로서의 퀴나졸린 | |
KR101877187B1 (ko) | 치환된 다이하이드로이소퀴놀린온 화합물 | |
TWI421078B (zh) | 關卡激酶抑制劑及其用途 | |
ZA200600693B (en) | Combination of mGluR2 antagonist and AChE inhibitor for treatment of acute and/or chronic neurological disorders | |
WO2018234805A1 (en) | SMALL MOLECULAR MODULATORS OF HUMAN STING | |
CA3005918C (en) | Octahydropyrrolo[3,4-c]pyrrole derivatives and uses thereof | |
JP2013525476A (ja) | Alk阻害剤としての複素環式誘導体 | |
TW202039489A (zh) | Mat2a之雜雙環抑制劑及用於治療癌症之使用方法 | |
WO2017049462A1 (zh) | 一类新型的flt3激酶抑制剂及其用途 | |
JP2006077023A (ja) | 多環式グアニン誘導体ホスホジエステラーゼv阻害剤 | |
WO2009070583A1 (en) | Pyrido[3,2-e]pyrazines, process for preparing the same, and their use as inhibitors of phosphodiesterase 10 | |
CN102596962A (zh) | Jak抑制剂 | |
TW200940548A (en) | Fused heterocyclic derivative and use thereof | |
EP3209651A1 (en) | Carbazole derivatives | |
JP2021528401A (ja) | Malt1阻害剤としてのピラゾール誘導体 | |
JP2016511262A (ja) | 置換二環式ジヒドロピリミジノン及び好中球エラスターゼ活性の阻害薬としてのそれらの使用 | |
JP6515175B2 (ja) | 芳香族ヘテロ環誘導体及びその医薬的適用 | |
JP2024502886A (ja) | がんを処置及び/又は予防するためのsos1阻害薬の医薬組合せ | |
KR20190129034A (ko) | 금속효소 억제제 화합물 | |
JP2008500979A (ja) | mGlu5レセプターアンタゴニストとしてのピリジン−4−エチニル−イミダゾール及びピラゾール | |
AU2013279040B2 (en) | Pharmaceutically active compounds | |
ZA200304557B (en) | Tetrahydro-(benzo or thieno)-azepine-pyrazine and triazine derivatives as mGluR 1 antagonists. |